Lipid rafts: evidence of biosyntax and biopragmatics

Information theorist Werner Gitt has proposed that information is best understood
within a multidimensional framework. This framework has five dimensions: the statistical,
syntactic, semantic, pragmatic and apobetic. Current evolutionary views of information
and biology are largely restricted to the statistical dimension. Alex Williams has
recently argued that the inheritance of biological information should be understood
within this multidimensional Gittian framework and has emphasised that extra-nuclear
cell structure may contribute to the information content of cells. In this article
I show that the emerging concept of ‘lipid rafts’ in cell membranes
represents both a syntactic and a pragmatic information structure within the cell.
As such they illustrate the existence of a higher order of organisation within the
cell than traditionally understood and provide strong support for the Gittian creationist
concept of how information is structured and inherited in biology.

* Terms marked with an asterisk are defined in the Glossary at
the end of this article.

Figure 1. Diagram showing some of the lateral organisation involved
in lipid raft domains. The outer plasma membrane leaflet has a heterogeneous arrangement
of cholesterol and sphingolipids. They appear to congregate into patches that have
distinct biophysical properties. This enables control of the lateral organisation
of membrane-bound proteins based on their phosphorylation and activation states
and the presence or absence of specific lipid anchors.

Werner Gitt has described information in terms of statistics, syntax, semantics,
pragmatics and apobetics.1
Within this theory, the lower levels of information are hierarchically arranged
in order to express the higher levels: i.e. statistics, syntax, semantics and pragmatics
are arranged in such a way as to express the apobetics or purpose, within
the organism (endowed by its Creator). In an analogy with linguistics, this is equivalent
to words, sentences, paragraphs and context being arranged in such a way that the
intended meaning (endowed by the author) may be conveyed, understood and
acted upon.

This contrasts sharply with the evolutionary position, which denies that any purpose
exists in biology. In the ‘selfish gene’ theory, for example, the ‘appearance
of purpose’ is considered to be nothing more than a consequence of natural
selection. Genes are believed to be the descendants of a hypothetical primordial
‘replicator’ that originated life and produced all of life’s variety
simply by natural selection favouring different combinations in different environments.
Information in this theory is nothing more than a serendipitous accumulation of
statistical errors that happen to have survival value for the genes.

Conversely, the Gittian information framework, and creationists in general, interpret
genetics and other biological processes in terms of their roles in enabling purpose
to be fulfilled. The most important purposes expressed in biology are for organisms
to reproduce after their kind, for humans to bear God’s image and worship
Him, and to fill the earth and subdue it.

If Gitt’s information framework is applicable to biology then there should
be evidence of information operating at the levels of syntax, semantics and pragmatics
within biological systems. Alex Williams has recently described these features within
a key area of genetics.2
He proposes that the nucleotide sequence found in DNA represents statistical information,
the amino acids specified by codons represent a semantic arrangement, the sequence
of amino acids represents a syntactic arrangement, and the function of gene products
represents a pragmatic arrangement. This description is appropriate but is incomplete
because gene products do not simply operate pragmatically but also form syntactic,
semantic and pragmatic arrangements within ever more complex processes that make
up the whole living organism.

In addition, Williams also highlighted the importance of structural modes
of inheritance, including cellular architecture, as providing a basis for the stasis
that is a major characteristic of inheritance and which forms part of the apobetic
purpose of reproducing after like kind.3

Understanding the interpretative machinery of the cell is an important step in beginning
to describe the way in which non-sentient entities, such as cells, translate abstract
information into action without conscious will.

In this article, I will show that the emerging concept of lipid rafts and their
function as cell-signalling platforms can be understood as both a syntactic and
a pragmatic arrangement of proteins and lipids and that this is derived from an
interaction between genetic and epigenetic factors*. As
such, they constitute a ‘molecular context’ or ‘cellular paragraph’
within which meaning is conveyed. Within the so-called ‘semiotic triad’
of object, sign and interpreter,4,5 lipid rafts form part of the
interpretive machinery of the cell that allows the meaning of the symbol to be defined
and connected to an appropriate response. Understanding the interpretative machinery
of the cell is an important step in beginning to describe the way in which non-sentient
entities, such as cells, translate abstract information into action without conscious
will. The interpretative machinery of the cell closely resembles Gitt’s description
of operational information.1 It is therefore apparent that lipid
rafts form part of an operational information structure within the cell.

Lipid rafts

The term ‘lipid raft’ is used to describe areas of cell membranes that
are selectively enriched in cholesterol, sphingolipids*
and signalling proteins* . Since Simons and Ikonen brought
attention to the possibility of their existence in 19976 there has been an explosion in efforts to detect
and characterise these curious structures.7
They are believed to form functional domains on the outer leaflet of cell membranes
that selectively include or exclude particular proteins depending on their levels
of phosphorylation* , activation or the presence or absence
of important ‘lipid tails’. In addition, lipid rafts are believed to
somehow connect to intracellular signalling and structural proteins and influence
their activities. Lipid rafts may thus concentrate members of different signalling
cascades* within a discrete area of the cell allowing the
components of the pathway to be in the right place at the right time.7

Do lipid rafts exist?

Although there are several lines of evidence that argue for the existence of lateral
arrangements of cholesterol, sphingolipids and proteins,8 some of the techniques used to study them may artificially
congregate these elements (e.g. detergent extraction)9,10
while other techniques have produced mixed results (e.g. fluorescent microscopy).11–14 Nevertheless, the weight of evidence
seems to suggest that lateral organisation of the outer leaflet of the cell membrane
occurs in vivo.

What are lipid rafts comprised of?

The plasma membrane* is composed of two phospholipid layers
with the hydrophobic hydrocarbon* chain ‘tails’
facing each other and the hydrophilic* polar*
‘head groups’ facing the internal and external surfaces. Membranes have
long been known to also contain proteins, cholesterol, sphingolipids (including
the class of glycosphingolipids known as gangliosides), and other components. It
has only recently been proposed that these various components do not exist completely
randomly or evenly across the plasma membrane surface but that there is a level
of lateral organisation. Thus there is evidence that sphingolipids and cholesterol
are relatively concentrated in ‘rafts’ in the outer leaflet of the membrane
and that proteins may have a preference for either the raft or non-raft regions
depending on the biophysical properties of the protein in question. See figure 1.

This lateral arrangement is controlled in part by the levels of cholesterol and
glycolipids, including gangliosides. Gangliosides are glycosphingolipids with one
or more sialic acid* residues and are often used as markers
of lipid raft domains. Their biosynthesis and regulation is complex (indeed it constitutes
another cellular process that displays syntax, semantics and pragmatics!) and it
is worth noting that they are not directly encoded in the genome since they are
not proteins. They require the cooperative action of several enzyme complexes to
construct them, direct them to their appropriate location and to maintain their
presence in the outer plasma leaflet.15–22
The hydrophobic ceramide* tails, the hydrophilic sugar residues
and the high levels of cholesterol mean that lipid raft domains have distinct physicochemical
properties compared with neighbouring non-raft membrane.

What do lipid rafts do?

Lipid rafts have been implicated in a plethora of cellular processes. The common
mechanism thought to underlie their function in most cases is their ability to preferentially
concentrate or exclude molecules of cell signalling cascades.7 This ability
is a result of the different biophysical properties of raft and non-raft membrane
and the changes in chemical properties of proteins upon activation, phosphorylation
or other events. For example, immunoglobulin E (IgE) signalling forms part of the
allergic immune response and is activated when IgE binds to Fc receptors*
(FcR) present on the plasma membrane of mast cells* . This
probably increases the partitioning of the FcR into lipid rafts with subsequent
cross-linking of FcR-bound IgE leading to phosphorylation of the FcR. This can then
initiate secondary downstream signalling events including the release of histamine* .23
Other signalling pathways are proposed to operate in a similar manner with lipid
rafts acting as concentrating platforms.24–26

Lipid rafts as biosyntax

Within written language systems, syntax refers to the set of rules that govern the
way in which semantic objects (words) are positioned with respect to one another,
how they may be joined together and how they may be modified while still retaining
the intended meaning. For example the statement: ‘Does John like Rosalyn?’
differs from the statement ‘John does like Rosalyn!’ only in word order
and punctuation. However, the change in order of the first two words changes the
meaning (semantics) and purpose (apobetics) of the statement from being a question
designed to elicit an answer to being a statement that answers a question. There
is no statistical difference between the information content of the two statements
(since they contain the same letters, words and spaces) but they differ at the level
of syntax and consequently at the semantic, pragmatic and apobetic levels.

Figure 2. Lipid rafts as biosyntax. An example of how lipid rafts
contribute to molecular syntax within cells. The binding of NRG to ErbB4 does not
exert any physiological changes under conditions in which lipid rafts are not allowed
to form. When lipid raft domains are allowed to form, NRG-ErbB4 translocates into
rafts along with other key components of the ERK signalling pathway including Shc
and Grb2. This allows the otherwise ‘meaningless’ arrangement of receptors
and signalling proteins to exert a physiological function and thus have semantic
and pragmatic meaning. In this manner lipid rafts function as a component of a molecular
syntax that defines the arrangement and meaning of symbols within a code.

In a similar manner, lipid rafts can be seen to contribute to a molecular syntax
within the cell. For example, it has been shown that in cultured cortical neurons* , the activation of the transmembrane signalling molecule
ErbB4 by its ligand neuregulin (NRG) induces the translocation of ErbB4 and adaptor
signalling molecules* into lipid raft domains from non-raft
domains.27 Furthermore,
this translocation into lipid rafts is required for NRG to exert its downstream
effects, including activation of the protein kinase ERK. When lipid rafts are disrupted,
the effects of NRG-induced activation of ErbB4 are not seen.

This situation is analogous to the sentences discussed above where the same words
mean something different when the syntax is altered. The two conditions, ‘ErbB4
in lipid rafts’ and ‘ErbB4 not in lipid rafts’, differ only in
the relative position of the relevant components of the system and not in the presence
or absence of these components. The lipid rafts do not change the statistics of
the information in the signalling pathway. Instead, they form a context in which
the arrangements of the members take on defined meanings. Thus in these cultured
cortical neurons, lipid rafts provide the molecular syntax in which NRG-induced
activation of ErbB4 can bring about particular effects that do not occur in their
absence (figure 2).

Lipid rafts as biopragmatics

Another example involving ERK signalling illustrates the way in which lipid rafts
can act in the role of molecular pragmatics. In linguistics, semantics deals with
the range of possible meanings of words and in biology it refers to the range of
possible functions of molecules. Syntax, as we have seen above, deals with the different
ways that components can be arranged to activate those meanings. Pragmatics, on
the other hand, is all about context. An author identifies a particular
intended meaning by the context in which he/she uses a word, and in biology, the
particular function of a molecule is also specified by the context. In
this example, the protein molecule CD45 has two quite different cellular functions
depending on its arrangement within or outside of lipid rafts.

Figure 3. Lipid rafts as biopragmatics—defining the effects
of the protein CD45. Some CD45 is located outside lipid rafts and is linked to ERK
activation and stimulation of IL-2 production. There is also some CD45 that is found
within lipid raft domains and is linked to antagonism of IL-2 production. The molecular
basis of this remains unclear, but it may be that different sets of signalling proteins
are preferentially linked to raft and non-raft membrane domains. This arrangement
constitutes a molecular pragmatics that allows a single molecule to take on different
‘meanings’ depending on its context.

Zhang and colleagues have shown that membrane compartmentalisation of the transmembrane
protein tyrosine phosphatase CD45 is an important feature in the regulation of T
cell activation* in the mouse.28 These authors found that a proportion of CD45
is found within lipid rafts and a proportion is found outside lipid raft domains.
The raft-localised CD45 was found to antagonise IL-2 production (IL-2 is a cytokine
involved in several important immunological processes) while the CD45 located outside
lipid rafts played a role in promoting IL-2 production via ERK activation.

There is evidence that during the stimulation of T cells, raft-associated CD45 is
excluded from these domains. This presumably leads to less inhibition of IL-2 and
greater stimulation of IL-2 via ERK. Thus a single molecule can have opposite
effects (stimulate or inhibit IL-2 production) depending on the molecular context
within which it operates (i.e. within or outside of lipid rafts) (figure 3).

The mechanisms linking CD45 signalling to IL-2 stimulation or inhibition are not
well understood, but it is likely that the raft and non-raft membrane domains contain
different proteins comprising distinct intracellular signalling cascades. Lipid
rafts act as a component of this molecular context and so contribute to the pragmatics
of the cell.

Inheritance of lipid rafts

Lipid rafts are components of cell membranes comprising of lipids and proteins.
As such, they are passed on from parent cell to daughter cell during cell division
as part of the cellular architecture that each cell inherits. In addition, the proteins
that contribute to their formation and maintenance (e.g. the enzymes involved in
ganglioside biosynthesis) are inherited both epigenetically as proteins in the lipid
bilayer, and genetically as genes on chromosomes in the nucleus. This means that
lipid rafts are passed on fully established and operational in an epigenetic manner,
while the relevant information for their maintenance is passed on in a genetic manner.
This illustrates how inheritance of the organised membrane structure forms part
of the cellular basis of stasis of the created kind, as Williams has hypothesised.3

Cell autonomy

Syntax, semantics and pragmatics are used in language by intelligent beings according
to conventions that allow purpose or apobetics, to operate. This requires
an ongoing conscious tie between the language symbols and their referents. But the
control and communication that operates within and between cells goes on autonomously
without an ongoing conscious tie between symbols (e.g. DNA sequence, cell-signalling
proteins, etc) and their referents (e.g. protein sequence, effectors of cell-signalling
pathways, etc). Instead, the ties between object, sign and interpreter are established
and maintained by an inherited information-based control system that operates according
to biochemical laws.

Could such information-based cellular life have arisen via the ‘selfish gene’
replicator mechanism? It would seem not, because a gene can only use its information
if it is part of a mechanism that contains transcription, translation and implementation
facilities (i.e. a cell).

Could such information-based cellular life have arisen via the ‘selfish gene’
replicator mechanism? It would seem not, because a gene can only use its information
if it is part of a mechanism that contains transcription, translation and implementation
facilities (i.e. a cell). So when lipid rafts are observed to function as syntactic
and pragmatic information structures in cells it points to an intelligent rather
than random original source.

Conclusion

The existence and operation of the lipid rafts in cell membranes can be seen as
an implementation of syntax and pragmatics in order to enable apobetics to operate
in the biological world in the absence of an ongoing conscious tie between object,
sign and interpreter by the cell. It therefore supports the notion that the multidimensional
framework of information of Werner Gitt is applicable to biological systems. Since
this understanding of information requires an intelligent source, observing it in
biological systems suggests their origin in an intelligent source rather than random,
unintelligent statistical processes.

The Gittian view of information emphasises apobetics as the ultimate controlling
factor in information-processing systems. This highlights the need to understand
biology from the perspective of ‘apobetics-down’ (i.e. the purpose-orientated
creationist perspective), rather than from the perspective of ‘statistics-up’
(i.e. the gene-orientated evolutionary perspective). There is a fresh need for a
biblically derived apobetic theology of biology which provides a purpose-oriented
framework for understanding biological processes and the nature of bioinformation.
Such a theology would need to define the key purposes of creatures and relate these
to biological processes, and would provide a philosophical foundation for studying
the information present in organisms.

Glossary

Adaptor signalling molecules:

Proteins and other molecules that connect extracellular signals to intracellular
signalling cascades.

Ceramide:

an N-acyl sphingosine which forms the lipid portion of glycosphingolipids.

Cortical neurons:

nerve cells from the cortical region of the brain.

Epigenetically:

information inherited via genes is inherited genetically. Information inherited
in any other way is inherited epigenetically.

Fc receptors:

the portion of an immunoglobulin molecule that initiates its effector functions
(e.g. complement activation, opsinisation, etc).

Histamine:

Derived from an amino acid, histamine is a chemical messenger involved in initiating
many of the events involved in acute inflammation.

Hydrocarbon:

an organic molecule which consists of carbon and hydrogen atoms.

Hydrophilic:

having an affinity for water. By contrast, hydrophobic means lacking an affinity
for water.

Mast cells:

an immune cell residing in connective tissue. It releases several substances, including
histamine, involved in acute inflammatory reactions.

Phosphorylation:

the addition of a phosphate group to a protein molecule. This often alters protein
structure and function and acts as a regulatory switch.

Plasma membrane:

the lipid layer which comprises the outer wall of each individual cell.

Polar:

the hydrogen bonding end of the phospholipid molecule, which is hydrophilic.

Sialic acid:

A 9 carbon acidic sugar. It is present on many glycolipids and glycoproteins and
is responsible for much of the negative charge on cell surfaces.

Signalling cascades:

series of reactions which occur as a result of a single stimulus.

Signalling proteins:

proteins which contribute to the transfer of information from cell to cell.

Anthony P said “Thanks for your … website, it’s really easy to navigate and it is a massive bonus to be able to read back-issues of your magazines … without your ministry I probably wouldn’t be a Christian today. Thank you so much and keep up the good work.” So help us do just that! Support this site